Endocarditis

I. What Every Physician Needs to Know.

This chapter summarizes the American Heart Association (AHA) and Infectious Disease Society of America (IDSA) guidelines for infectious endocarditis (IE), with a focus on the key points for the front-line clinician.

Infective endocarditis (IE) is relatively uncommon, but this is difficult to determine because few diagnosed cases are "definite." Manifestations of disease vary widely and so it can be seen in almost any medical subspecialty.

Pathogenesis requires both alterations in the valvular endothelial surface and other factors to produce pathology.

Management depends on the causative organism and whether the patient has native or prosthetic valve endocarditis. These factors affect drug choices, length of therapy, and the need for surgery.

Recent changes in the rates of resistant organisms have made some aspects of treatment more complicated than what is noted historically.

II. Diagnostic Confirmation: Are you sure your patient has Endocarditis?

The Duke Criteria for diagnosing endocarditis should be used when suspected. See Figure 1.

Figure 1.

(Left table): Definition of IE according to the modified Duke criteria (Right table): Major/minor criteria in the modified Duke criteria for the diagnosis of IE.

Suspected IE can fall under three categories:

Definite (2 major criteria, 1 major and 3 minor, or 5 minor criteria);

Possible (1 major and 1 minor criteria, or 3 minor criteria);

Rejected (firm alternative diagnosis, resolution of IE syndrome with antibiotic therapy for less than or equal to 4 days, no pathologic evidence of IE at surgery or autopsy, or does not meet the above criteria).

The Duke criteria should be used as a clinical guide, but the clinician should always use his/her best judgment since IE can present itself in such varied ways.

Diagnosis is made by blood cultures and echo findings. Note that Coxiella burnetii can be diagnosed by blood culture or anti-phase 1 IgG antibody titer.

B. History Part 2: Prevalence.

It is difficult to estimate the exact incidence of IE. Hospital admissions for endocarditis in one study looking at hospitals within the US from 1998-2009 noted that the rate rose from approximately 25,000 to approximately 39,000 in 2009.

Incidence: Men > Women (generally 1.7:1, but can range from 1:1 or 3:1) although in patients age <35, Women>Men.

IE has become more common in the elderly although the rise in incidence in the US is not explained by an aging population alone.

IE is more common in patients with a history of valvular disease, IE, prosthetic valves, intravenous drug abuse (IVDA), indwelling IV catheters, pacemakers with intracardiac leads, ESRD on HD, and congenital heart disease.

C. History Part 3: Competing diagnoses that can mimic Endocarditis.

This list could be made much longer, but these are simply to mention just a few:

Bacteremia without IE.Viral Hepatitis.Lyme disease.Sepsis: Difficult to distinguish in the short-term as both are fulminant infections. An echo and the causative organism would help distinguish between these infections.Abdominal abscess.Osteomyelitis.Malignancy.Atrial myxoma.Autoimmune and Connective tissue diseases: Differentiating requires respective laboratory and biopsy results.Hereditary fever syndromes: Distinguishing between these and IE would depend on the specific entity suspected.Tuberculosis.

D. Physical Examination Findings.

A complete and thorough physical exam should look especially for any following:

Physical exam findings in IE can also be non-specific and given the shift in epidemiology (Staph is now more common than Strep as a causative organism likely leading to more acute rather than subacute onset of disease), some physical findings may not be as prevalent as previously noted (since there may not be enough time for immunologic phenomenon to occur).

Figure 5.

Osler nodes.

Figure 6.

Splinter hemorrhage.

Roth spots appear to be a hemorrhage in the retina with a white center. They can also be seen in leukemia, DM, and collagen vascular diseases. See Figure 7.

Figure 7.

Roth spot.

E. What diagnostic tests should be performed?

Blood cultures should be obtained before antibiotic therapy if possible. At least three sets of cultures should be taken from different venipuncture sites and at different times – the first and the last set should be drawn at least 1 hour apart from each other. More specimens may be necessary if the patient has had antibiotics within the last 2 weeks.

Echocardiograms should be performed expediently. See Figure 8 and Figure 9.

Figure 8.

Approach to the use of Echocardiograms.

Figure 9.

Use of echocardiography during diagnosis and treatment of IE.

The risk for embolization of vegetations is highest >10 mm in diameter and on the anterior mitral leaflet. However, it is important to note that some researchers have found that Staph or fungal IE have a high rate of embolization regardless of vegetation size.

A TEE is the preferred image modality, but a TTE is reasonable if TEE is unable to be obtained in a timely fashion. Of note, a TTE could be more useful in detecting lesions in right-sided IE.

Repeat TEE 7-10 days after an initially negative result if there is still a high IE suspicion. Also reasonable in patients with worsening clinical problems or unchanging symptoms (patient is still febrile despite several days of appropriate antimicrobial therapy).

After completion of therapy, a TTE should be obtained to determine the new baseline for the patient.

EKG - look for signs of heart block which could be a sign of a perivalvular abscess.

CXR - look for signs of septic pulmonic emboli especially in an IVDA and signs of right sided IE. See Figure 10.

Figure 10.

CXR w/signs of septic emboli.

Consider targeted computed tomography (CT) and/or magnetic resonance imaging (MRI) imaging of various parts of the body if one is suspicious for embolisms. Given the high incidence of neurologic complications, cerebrovascular imaging may be considered in all patients with left-sided IE even if the patient has no neurologic signs or symptoms.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Blood cultures should be obtained before antibiotic therapy if possible. At least three sets of cultures should be taken from different venipuncture sites and at different times – the first and the last set should be drawn at least 1 hour apart from each other. More specimens may be necessary if the patient has had antibiotics within the last 2 weeks.

The yield of blood cultures is increased when an increased volume of blood is drawn.

The patient does not need to be febrile in order to take cultures because most patients have a fairly constant low-grade bacteremia.

Blood cultures should be held for at least 3-4 weeks because some organisms are slow-growing.

Some organisms require special media in which to grow (e.g., - nutritionally variant streptococci). Infectious disease (ID) consultation should be obtained in all patients who are to be started on therapy for suspected IE, and can help determine what special conditions/media are required given the patient and circumstances.

Patients with "subacute" IE may not have a significant leukocytosis, but those with more acute cases are more likely to have high WBC counts. Anemia is also common (70-90%), but nonspecific. Thrombocytopenia occurs in 5-15% (more common in neonatal IE).

If the patient has surgery, valve culture and valve histopathology should be obtained.

One can consider the following lab tests, but many are nonspecific and the diagnostic utility is limited:

An antiphase I IgG titer of >1:800 for Coxiella burnetii is one of the major criteria for diagnosing IE. However, this organism is a relatively uncommon cause of IE.

A rheumatoid factor can be checked as this is also part of the Duke minor criteria. More likely to be positive in subacute cases when the duration is >6 weeks.

ESR is elevated in 90-100% of cases, but this is a nonspecific finding. The same can be said for a CRP.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Please refer to Figure 9for the use of echocardiograms in IE.

The risk for embolization of vegetations is highest >10 mm in diameter and on the anterior mitral leaflet. However, it is important to note that some researchers have found that Staph or fungal IE have a high rate of embolization regardless of vegetation size.

A TEE is the preferred image modality, but a TTE is reasonable if TEE is unable to be obtained in a timely fashion.

Repeat TEE 7-10 days after an initially negative result if there is still a high IE suspicion. This would also reasonable in patients with worsening clinical problems or unchanging symptoms (patient is still febrile despite several days of appropriate antimicrobial therapy).

After completion of therapy, a TTE should be obtained to determine the new baseline for the patient.

EKG - look for signs of heart block which could be a sign of a perivalvular abscess.

CXR - look for signs of septic pulmonic emboli especially in an IVDA and signs of right sided IE. See Figure 10.

Consider targeted CT and/or MRI imaging of various parts of the body if one is suspicious for embolisms. Given the high incidence of neurologic complications, cerebrovascular imaging may be considered in all patients with left-sided IE even if the patient has no neurologic signs or symptoms.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

ESR is elevated in 90-100% of cases, but this is a nonspecific finding. The same can be said for a CRP.

III. Default Management.

Consider surgery in the following:

1. Blood cultures should be obtained before antibiotic therapy if possible. At least three sets of cultures should be taken from different venipuncture sites and at different times – the first and the last set should be drawn at least 1 hour apart from each other. More specimens may be necessary if the patient has had antibiotics within the last 2 weeks.

EKG: look for signs of heart block which could be a sign of a perivalvular abscess.

CXR: look for signs of septic pulmonic emboli especially in an IVDA and signs of right sided IE. See 1. Figure 10.

2. Initiate antimicrobial therapy immediately if acutely ill. The choice of empiric therapy will depend on the patient demographics, history of prosthetic valve, currently clinical condition, previously administered antibiotics, and previous microbiologic history (e.g., pt has a history of MRSA, would give vancomycin as part of treatment strategy). Consult ID for guidance on initial therapy.

3. Obtain echocardiogram. See 3. Figure 9.

The risk for embolization of vegetations is highest if >10 mm in diameter and on the anterior mitral leaflet.

A TEE is the preferred image modality, but a TTE is reasonable if TEE is unable to be obtained in a timely fashion.

Repeat TEE 7-10 days after an initially negative result if there is still a high IE suspicion. Also reasonable in patients with worsening clinical problems.

After completion of therapy, a TTE should be obtained to determine the new baseline for the patient.

4. Recommend ID consultation. Consider surgical consultation depending on the likelihood of surgical necessity. All patients with a history of CHF (regardless of mechanism) should have a surgical consultation.

5. Consider targeted CT and/or MRI imaging of various parts of the body if suspicious for embolic phenomenon.

6. Await results of blood culture findings. Tailor antibiotics to the organism and whether the patient has a prosthetic valve.

Please refer to AHA and IDSA guidelines for antibiotic selection for specific organisms.

Daptomycin is another option that is often used in patients with IE with resistant Gram positive organisms. It has been approved by the US Food and Drug Administration (FDA) for the treatment of Staphylococcus aureus bacteremia and right sided Staphylococcus aureus IE.

7. Determine whether the patient needs valve replacement surgery. ID as well as cardiothoracic surgery should be consulted if this is a possibility.

The threshold for operating in prosthetic valve IE is generally much lower than native valve IE.

General indications for surgery in native valve endocarditis include the following:

CHF (especially if it is mod-severe) directly related to valve dysfunction.

More than one serious systemic embolic episode despite appropriate antibiotic therapy during the first 2 weeks of therapy.

Uncontrolled infection (persistent bacteremia for >5-7 days provided other areas of infection and fever have been excluded) after starting appropriate antimicrobial therapy.

8. Repeat blood cultures 48-72 hours after antibiotic therapy to determine if bacteremia has "cleared.". If still bacteremic, repeat blood cultures every 24-48 hours until bacteremia has resolved.

If prolonged bacteremia, a CT and/or MRI of the chest / abdomen / pelvis may be appropriate to see if there are signs of an abscess or other nidus of infection causing ongoing bacteremia.

If still bacteremic 7 days after starting appropriate antibiotic therapy, the patient likely needs valve replacement.

9. When bacteremia has cleared, the patient is clinically stable, and the patient is taking antibiotics he/she can tolerate, place PICC line and order outpatient antibiotics.

Weekly labs should be drawn to look for toxicities.

10. The patient should receive antibiotic prophylaxis in the future if a dental procedure, certain respiratory/GI/GU tract procedures, and certain skin and musculoskeletal tissue procedures. See antibiotic prophylaxis chapter 5053.

A. Immediate Management.

1. Blood cultures should be obtained before antibiotic therapy if possible. At least three sets of cultures should be taken from different venipuncture sites and at different times – the first and the last set should be drawn at least 1 hour apart from each other. More specimens may be necessary if the patient has had antibiotics within the last 2 weeks. A minimum of 10mL (preferably 20mL) should be taken from adults per bottle and 0.5 to 5 mL from infants and children.

EKG: look for signs of heart block which could be a sign of a perivalvular abscess.

CXR: look for signs of septic pulmonic emboli especially in an IVDA and signs of right sided IE. See Figure 10.

2. Initiate antimicrobial therapy immediately if acutely ill. Note that immediate empiric therapy is not always necessary if the patient does not have acute symptoms. Consult ID for guidance on initial therapy.

3. Obtain echocardiogram. See Figure 9.

The risk for embolization of vegetations is highest if >10 mm in diameter and on the anterior mitral leaflet.

A TEE is the preferred image modality, but a TTE is reasonable if TEE is unable to be obtained in a timely fashion.

Repeat TEE 7-10 days after an initially negative result if there is still a high IE suspicion. Also reasonable in patients with worsening clinical problems.

After completion of therapy, a TTE should be obtained to determine the new baseline for the patient.

4. Recommend ID consultation. Consider surgical consultation depending on the patient's likelihood of surgical necessity. All patients with a history of CHF (regardless of mechanism) should have a surgical consultation.

B. Physical Examination Tips to Guide Management.

Cardiac findings include new regurgitant murmur or signs of new onset heart failure.

Await results of blood culture findings. Tailor antibiotics to the organism and whether the patient has a prosthetic valve.

Repeat blood cultures 48-72 hours after antibiotic therapy to determine if bacteremia has "cleared." If still bacteremic, repeat blood cultures every 24-48 hours until bacteremia has resolved.

A BMP should be checked periodically to ensure that renal function remains stable. CBC should also be checked periodically since many antimicrobials can have effects on the hematologic system.

Other specific lab tests that need to be ordered will depend on what antibiotic is used (oxacillin – ALT/AST/Alk phos; daptomycin – creatine kinase; vancomycin - vancomycin trough, etc.).

D. Long-term Management.

When bacteremia has cleared, the patient is clinically stable, and the patient is taking antibiotics he/she can tolerate, place PICC line and order outpatient antibiotics.

Weekly labs should be drawn to look for toxicities.

After completion of therapy, a TTE should be obtained to determine what is the new baseline for the patient.

The patient should receive antibiotic prophylaxis in the future if a dental procedure, certain respiratory/GI/GU tract procedures, and certain skin and musculoskeletal tissue procedures. See antibiotic prophylaxis 5053.

E. Common Pitfalls and Side-Effects of Management.

The most common pitfall is giving of antibiotics before adequate blood culture specimens are obtained since this significantly reduces the diagnostic yield.

If valve replacement surgery is something that seems likely, early involvement of cardiothoracic surgery is important as oftentimes earlier surgical intervention lead to improved outcomes.

Nephrotoxicity (ranging 5-25% of cases; however, most of the doses used in the treatment of IE are lower than what is given when aminoglycosides are given as a single agent. The difference is synergistic dosing).

Cochlear toxicity (incidence 3-14%).

Vestibular toxicity.

Neuromuscular blockade (exceedingly rare).

Rifampin side-effects:

Multiple drug-drug interactions (too many to list here).

Abdominal pain, nausea, vomiting.

Transaminitis (incidence is low, but increased risk in patients with chronic liver disease).

Mild thrombocytopenia, leukopenia, granulocytopenia.

Uveitis.

Rash, hypersensistivity reactions.

Lupus-like syndrome.

Discoloration of sweat, tears, urine, and other bodily fluids.

Linezolid side-effects:

Reversible myelosuppression (occurs usually 2 weeks or more into therapy. Thrombocytopenia is most common, but anemia and neutropenia can also occur).

Serotonin syndrome (linezolid is a MAO-inhibitor).

Optic neuritis, blurred vision.

Nausea, vomiting, diarrhea, constipation.

Rash.

Dizziness.

Headache.

Daptomycin side-effects:

Muscle toxicity (associated with rhabdomyolitis).

Paresthesias, dysesthesias and peripheral neuropathies.

Can cause a falsely elevated INR level.

Quinupristin-dalfopristin side-effects:

Phlebitis (especially if given in a peripheral IV; Quinupristin-dalfopristin is preferably given through central access).

Arthralgias (9.1%) and myalgias (6.6%): these can be severe, but the CK will be normal: increased risk in patients with chronic liver disease, elevated bilirubin, liver transplant patients, and those taking mycophenolate and cyclosporine.

1. When should clinic follow up be arranged and with whom?

2. What tests should be conducted prior to discharge to enable best clinic first visit?

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit?

Routine follow up labs taken weekly by home health to monitor drug toxicity.

E. Placement Considerations.

The patient should have a PICC line placed for central venous access for antibiotic therapy prior to discharge.

The patient will need to be in contact isolation if the patient is found to have a resistant organism as the cause of IE (MRSA) and is going somewhere other than home (nursing facility, rehab, long-term care center, etc.). Placement to a skilled nursing facility, subacute rehab, acute rehab, long-term acute care center will depend on the patient’s overall condition and functional status.

F. Prognosis and Patient Counseling.

Prognosis and complications of therapy are variable.

Death rates in patients with both native valve and prosthetic IE vary depending on the organism and the situation. For example, acute staphylococcal IE has ~25-40% mortality, but mortality rates are often greater than 50% if the patient is older than 50.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

None

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

The patient should receive antibiotic prophylaxis in the future if a dental procedure, certain respiratory/GI/GU tract procedures, and certain skin and musculoskeletal tissue procedures. See antibiotic prophylaxis chapter.

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